Synthesis, in vitro, and in vivo antibacterial activity of nocathiacin I thiol-Michael adducts

The synthesis and antibacterial activity of a series of nocathiacin I derivatives (4-20) containing polar water solubilizing groups is described. Thiol-Michael adducts containing acidic polar groups have reduced antibacterial activity whereas those with basic polar groups have retained very good antibacterial activity.     

N-Thiolated beta-lactam antibacterials: defining the role of unsaturation in the C4 side chain

N-Methylthio beta-lactams represent a novel family of antibacterial agents for methicillin-resistant Staphylococcus aureus (MRSA). The structure-activity functions and mechanism of action of these compounds, although still largely undefined, differ dramatically from those of all previously reported beta-lactam antibiotics. Prior work has established that the N-alkylthio moiety is required for antibacterial activity, and that a variety of unsaturated groups can be tolerated at C(4) of the lactam ring. This report describes the effect that unsaturation within the C(4) substituent has on antibacterial activity of these interesting new N-thiolated beta-lactams.     

Structure-activity relationships of novel antibacterial translation inhibitors: 3,5-diamino-piperidinyl triazines

Structure-activity relationships of the 3,5-diamino-piperidinyl triazine series, a novel class of bacterial translation inhibitors, are described. Optimization was focused on the triazine C-4 position in which aromatic substituents that contained electron-withdrawing groups led to potent inhibitors. The initial lack of antibacterial activity was correlated with poor cellular penetration. Whole cell antibacterial activity was achieved by linking additional aromatic moieties at the triazine C-4 position.     

Synthesis of N-alkylated derivatives of imidazole as antibacterial agents

N-Alkylation of imidazole, 2-methylimidazole and 2-methyl-4-nitroimidazole have been carried out to achieve effective antibacterial agents. The products were then investigated for antibacterial activity against Escherichia coil, Staphylococcus aureus and Pseudomonas aeruginosa. Antibacterial effects of 1-alkylimidazole derivatives increase as the number of carbons in alkyl chain increases up to nine carbons. Also substitution of 2-methyl and 2-methyl-4-nitro groups on imidazole ring increases the antibacterial activity.     

Synthesis and antibacterial activity of substituted flavones, 4-thioflavones and 4-iminoflavones

Synthesis of flavones, 4-thioflavones and 4-iminoflavones was carried out with the substitution of variable halogens, methyl, methoxy and nitro groups in the A, B and AB rings of the respective compounds and we also report here their antibacterial activity. Most of the synthesized compounds were found to be active against Escherichia coli, Bacillus subtilis, Shigella flexnari, Salmonella aureus, Salmonella typhi and Pseudomonas aeruginosa. Activity of 4-thioflavones and 4-iminoflavones was found to be higher than that of their corresponding flavone analogues. Investigated compounds having substituents like F, OMe and NO2 at 4'-position in ring-B exhibited enhanced activity and the presence of electronegative groups in the studied compounds showed a direct relationship to the antibacterial activity.     

Antibacterial and antifungal efficacy of surface functionalized polymeric beads in repeated applications

A simple method was developed to prepare polymeric microbeads with antibacterial and antifungal properties. The microbeads of approximately spherical shape and narrow size distribution were prepared from a mixture of poly (4-vinyl pyridine) (P4VP) and poly (vinylidene fluoride) (PVDF) by a phase inversion technique and subsequently derivatized with alkyl bromides having 4-10 carbon atoms. The quaternization of the pyridine groups into pyridinium groups confers the surface with highly effective and long-lasting antibacterial and antifungal properties, as shown by the effect on Escherichia coli and Aspergillus niger. Upon contact with the N-alkylated beads, the bacteria and fungal spores are lysed and intracellular constituents leach out into the medium. The efficacy of the alkyl chains in disrupting the cell membrane was investigated. The stability of the functional group and microbiocidal effectiveness of the microbeads in repeated applications was also assessed.     

Synthesis, structure, molecular docking, and structure-activity relationship analysis of enamines: 3-aryl-4-alkylaminofuran-2(5H)-ones as potential antibacterials

Thirty-one 3-aryl-4-alkylaminofuran-2(5H)-ones were designed, prepared and tested for their antibacterial activity. Some of them showed significant antibacterial activity against Gram-positive organisms, especially against Staphylococcus aureus ATCC 25923, but all were inactive against Gram-negative organisms. Out of these compounds, 3-(4-bromophenyl)-4-(2-(4-nitrophenyl)hydrazinyl)furan-2(5H)-one (4a11) showed the most potent antibacterial activity against S. aureus ATCC 25923 with MIC(50) of 0.42 μg/mL. The enzyme assay revealed that the possible antibacterial mechanism of the synthetic compounds might be due to their inhibitory activity against tyrosyl-tRNA synthetase. Molecular dockings of 4a11 into S. aureus tyrosyl-tRNA synthetase active site were also performed. This inhibitor snugly fitting the active site might well explain its excellent inhibitory activity. Meanwhile, this modeling disclosed that a more suitable optimization strategy might be to modify the benzene ring at 3-position of furanone with hydrophilic groups.     

Proline residue-modified polycationic analogs of gramicidin S with high antibacterial activity against both Gram-positive and Gram-negative bacteria and low hemolytic activity.

Novel polycationic analogs of the cyclic decapeptide antibiotic, gramicidin S, possessing NH(2), D/L-Phe-NH or L-Lys-NH groups at the 4alpha- or 4beta-positions of the L-Pro residues, were synthesized. While L-Pro(4alpha/beta-NH(2))-containing analogs exhibited much weaker antibacterial activity, the D/L-Phe and L-Lys-substituted analogs exhibited higher antibacterial activity against Gram-negative bacteria than the parent gramicidin S. All of these additional amino group-containing analogs showed substantially reduced toxicity against human blood cells.     

Preliminary evaluation of antimicrobial activity of diastereomeric cis/trans-3-aryl(heteroaryl)-3,4-dihydroisocoumarin-4-carboxylic acids

Preliminary differentiating screening of the antibacterial and antifungal activity of a series of diastereomeric cis/trans-3-aryl(heteroaryl)-3,4-dihydroisocoumarin-4-carboxylic acids (3a-i) was performed by the agar diffusion method against twelve microorganism strains of different taxonomic groups. S. aureus and A. niger were the most sensitive strains to the antibiotic effect of the tested compounds, both inhibited by 10 of 12 compounds. The most potent antibacterial agent was cis-3-phenyl-3,4-dihydroisocoumarin-4-carboxylic acid (cis-3a), exhibiting activity against all seven bacterial test strains.     

Design,synthesis and biological evaluation of potential antibacterial butyrolactones

Novel butyrolactone analogues were designed and synthesized based on the known lichen antibacterial compounds, lichesterinic acids (B-10 and B-11), by substituting different functional groups on the butyrolactone ring trying to enhance its activity. All synthesized butyrolactone analogues were evaluated for their in vitro antibacterial activity against Streptococcus gordonii. Among the derivatives, B-12 and B-13 had the lowest MIC of 9.38 μg/mL where they have shown to be stronger bactericidals, by 2–3 times, than the reference antibiotic, doxycycline. These two compounds were then checked for their cytotoxicity against human gingival epithelial cell lines, Ca9–22, and macrophages, THP-1, by MTT and LDH assays which confirmed their safety against the tested cell lines. A preliminary study of the structure–activity relationships unveiled that the functional groups at the C₄ position had an important influence on the antibacterial activity. An optimum length of the alkyl chain at the C₅ position registered the best antibacterial inhibitory activity however as its length increased the bactericidal effect increased as well. This efficiency was attained by a carboxyl group substitution at the C₄ position indicating the important dual role contributed by these two substituents which might be involved in their mechanism of action.     

Synthesis and antibacterial activity of novel and potent DNA gyrase inhibitors with azole ring

The 4-piperidyl moiety and the pyrazole ring in 1-(3-chlorophenyl)-5-(4-phenoxyphenyl)-3-(4-piperidyl)pyrazole 2, which has previously shown improved DNA gyrase inhibition and target-related antibacterial activity, were transformed to other groups and the in vitro antibacterial activity of the synthesized compounds was evaluated. The selected pyrazole, oxazole and imidazole derivatives showed moderate inhibition against DNA gyrase and topoisomerase IV with similar IC(50) values (IC(50)=9.4-25 microg/mL). In addition, many of the pyrazole, oxazole and imidazole derivatives synthesized in this study exhibited potent antibacterial activity against quinolone-resistant clinical isolates and coumarin-resistant laboratory isolates of Gram-positive bacteria with minimal inhibitory concentration values equivalent to those against susceptible strains.     

Synthesis and antibacterial activity of 4'-O-heteroarylcarbamoyl derivatives of macrolide

A series of novel 4'-position modified macrolide derivatives has been synthesized via a facile procedure. Their in vitro antibacterial activities against constitutively erythromycin-resistant strains were evaluated. Among the derivatives tested, compound 8a which has 11,12-carbamate and 4'-O-heteroarylcarbamoyl groups was found to have potent activity against most resistant bacteria.     

Antibacterial activity of a virgatusin-related compound

The relationship between antibacterial activity of tetra-substituted tetrahydrofuran lignans (1-4) and their absolute configurations was tested. Only compound 4 among two virgatusins and two related compounds exhibited growth inhibitory activity against the Gram-positive bacteria Bacillus subtilis, Staphylococcus aureus and Listeria denitrificans. Compound 4 affected the growth of B. subtilis in a bactericidic manner, and its ability to dissipate the cytoplasmic membrane potential was investigated using the fluorescence probe 3,3'-dipropylthiadicarbocyanine iodide. These results suggested that compound 4 damages cells by causing the loss of the proton motive force and disruption of the cellular integrity of the membrane, leading to cell death. In addition, it was shown that the antibacterial activity of a lignan was closely related to its absolute configuration and functional groups.     

Synthesis and antibacterial activity of a novel series of DNA gyrase inhibitors: 5-[(E)-2-arylvinyl]pyrazoles

The 2-arylvinyl moiety in 1-(3-chlorophenyl)-3-(4-piperidyl)-5-[(E)-2-(5-chloro-1H-indol-3-yl)vinyl]pyrazole 2, which has previously shown improved DNA gyrase inhibition and target-related antibacterial activity, was transformed to other groups and the in vitro antibacterial activity of the synthesized compounds was evaluated. Many of the 5-[(E)-2-arylvinyl]pyrazoles synthesized in this study exhibited potent antibacterial activity against quinolone-resistant clinical isolates of gram-positive bacteria with minimal inhibitory concentration values equivalent to those against susceptible strains.     

壳聚糖对大肠杆菌的抑制作用规律及抗菌机理初探

考察了不同分子量壳聚糖对大肠杆菌的抑菌性能,利用壳聚糖的席夫碱反应对其氨基加以保护,探讨了壳聚糖对大肠杆菌的抗菌机理。研究结果表明:壳聚糖分子量越小,对大肠杆菌的抗菌作用越明显;壳聚糖对大肠杆菌的抑菌作用与其氨基的质子化有关。     

北部湾近海珊瑚礁区系沉积物抗菌活性放线菌类群

通过对大肠埃希菌和枯草芽胞杆菌抗菌活性初步筛选,从北部湾近海珊瑚礁区5个沉积物样品中成功分离得到51株具有不同抗菌活性的放线菌,其中9株具有较强抗菌能力。根据这9株放线菌的菌落和孢子形态,可确定它们都属于链霉菌属。 RAPD-PCR分析表明这9株放线菌为6种不同类型,16S rDNA序列和系统发生树分析表明,9株放线菌可划分到4个大的类群6种不同类型,且结果显示RAPD-PCR聚类分析与16S rDNA序列聚类分析的结果具有较大的一致性。生理生化鉴定结果表明,分离株与亲缘关系最近的放线菌模式菌株的生理生化特征均存在差异,这说明分离株为放线菌新种的可能性比较大。这6种放线菌具有较为广谱的抑菌活性,并且抑菌活性均存在一定的差异,说明其可能分泌出多种结构功能不同的活性次生代谢产物。研究结果表明,广西北部湾近海珊瑚礁区系沉积物蕴藏着丰富的可供药物开发的放线菌资源。     

Preparation and characterization of durable antibacterial cellulose biomaterials modified with triazine derivatives

Cellulose fabric was chemically modified with the triazine derivatives containing the multi-cationic benzyl groups. The novel durable antibacterial cellulose biomaterial containing the multi-cationic benzyl groups was prepared. The chemical structure and thermal property of the antibacterial cellulose biomaterial were investigated with FT-IR spectra, nitrogen content analysis, and differential scanning calorimetry (DSC). The results show that the thermal stability of the novel antibacterial cellulose was slightly decreased. Physical properties of the novel antibacterial cellulose had not significant change. The novel antibacterial cellulose imparted excellent durable antibacterial properties.     

Antimicrobial and chemical detoxifying functions of cotton fabrics containing different benzophenone derivatives

Several benzophenone chromophoric groups were incorporated onto cotton fabrics by using 4-hydroxybenzophenone, 4,4′-dihydroxybenzophenone, 4-chloro-4′-hydroxybenzophenone, and 4-benzoylbenzoic acid as reagents. The fabric treatment was conducted by a pad-dry-cure method, and the benzophenone chromophoric group incorporated cotton fabrics were characterized and confirmed by FTIR. Tensile strengths of benzophenone chromophoric groups modified cotton fabrics were also measured. 4-Hydroxybenzophenone treated cotton fabric showed the most powerful antibacterial activity among all samples, and 4-benzoylbenzoic acid treated cotton fabric demonstrated pesticide degradation ability, under UV irradiation.     

负载金属离子的5A 沸石的体外抗菌实验

目的:探讨负载金属离子的5A沸石的体外抗菌作用。方法:选用金黄色葡萄球菌、铜绿假单孢菌、白色念珠菌,利用倍比稀释法对5A沸石组、磺胺嘧啶银组及载不同浓度Ag+、Zn2+5A沸石共15组进行了体外抗菌试验研究,确定最佳抗菌效果离子负载方案。结果:三种细菌的MIC,双金属离子负载在抗菌上具有协同载Ag+5A沸石分别达到了125μg/ml~500μg/ml、31.25μg/ml~500μg/ml、250μg/ml~500μg/ml;附载Zn2+5A沸石分别达到了12.5mg/ml~25mg/ml、6.25mg/ml~50mg/ml、25mg/ml;负载双离子5A沸石分别为250μg/ml~500μg/ml、62.5μg/ml~500μg/ml、500μg/ml。结论:5A沸石负载金属离子后均具有抗菌作用,且抗菌作用与附载金属离子的量正相关;负载相同质量Ag+的5A沸石较附载Zn2+者具有更强的抗菌作用;双金属离子负载在抗菌上具有协同作用;2%Ag++8%Zn2+与2%Ag++10%Zn2+及4%载银组与阳性对照组无显著性差异。     

Synthesis and biological activity of 1beta-methyl-2-[5'-isoxazoloethenylpyrrolidin-3'-ylthio]carbapenems

A new series of 1beta-methylcarbapenems 1a-i bearing isoxazoloethenyl groups on the pyrrolidine ring has been prepared and evaluated for in vitro antibacterial activity and stability to DHP-I. Most compounds showed excellent antibacterial activity and high stability to DHP-I superior to that of meropenem. Of these new carbapenems, 1a,b,h exhibited the best combination of antibacterial activity and DHP-I stability.